Clinical Outcomes and Cost-Effectiveness of Collaborative Dementia Care

This secondary analysis of a cluster randomized clinical trial investigates clinical outcomes and the cost-effectiveness of collaborative dementia care management compared with usual care among adults with dementia who live at home.


Introduction
Health care systems worldwide are experiencing resource constraints, which could cause poor adherence to recommended treatments. 1 This is especially the case for the increasing number of people living with dementia, who have high multimorbidity in addition to cognitive impairment 2 and require comprehensive multiprofessional support. 3,4neral practitioners (GPs) are responsible for identifying the first signs of cognitive decline and initiating dementia-specific diagnostics and treatment. 5However, primary care systems are unprepared to manage this complex postdiagnostic support. 61][12] Measures aimed at attenuating and alleviating symptom progression can enhance health-related quality of life (HRQOL), prolong autonomy in daily life for a person living with dementia, and conserve health care resources. 13,14llaborative dementia care management (CDCM) programs are defined as interventions delivered in the community to coordinate postdiagnostic, multiprofessional support in primary care for people living with dementia and their caregivers, considering their individual needs according to evidence-based guidelines. 3,15,16A meta-analysis across 13 randomized clinical trials conducted until 2011 revealed that CDCM was associated with delayed institutionalization, reduced behavioral and psychological symptoms over 18 months, and improved caregiver burden over 6 months. 17[20][21] All trials were limited to short observational periods.Evidence from methodologically rigorous studies over an extended time horizon (>24 months) is lacking.3][24] Promising results of delayed institutionalization over 12 and 18 months [18][19][20][21] could offset the cost-effectiveness if more institutionalizations occur later, but this is currently unknown.Therefore, the objective of this study was to evaluate, for the first time to our knowledge, the association of CDCM with patient, caregiver, and health system-relevant outcomes and the cost-effectiveness of CDCM compared with usual care over 36 months.

JAMA Network Open | Geriatrics
Clinical Outcomes and Cost-Effectiveness of Collaborative Dementia Care

Trial Design
This was a secondary analysis based on 36-month follow-up data from the DelpHi-MV GP-based cluster randomized clinical trials (NCT01401582), which was designed to test the efficacy of a CDCM in primary dementia care. 255][26][27][28][29] Reporting followed the Consolidated Standards of Reporting Trials (CONSORT) 30,31 and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 32 reporting guidelines.The trial was approved by the ethical committee of the Chamber of Physicians of Mecklenburg-Western Pomerania, Germany.Written informed consent was obtained.
For the trial, GP practices (n = 854) in Mecklenburg Western-Pomerania, a federal state in Germany, were invited to participate.A total of 136 GP practices that agreed to participate were randomized (1:1) to the intervention (CDCM) or the control group (usual care) by the study center using simple randomization without stratification or matching.
The GP practices were not informed about their randomization status but became aware of the randomization due to the nature of the intervention, likely causing a reduced recruitment motivation in practices in the control group and, thus, an imbalanced group distribution.The same nurses performed data assessment and interventions to reduce the burden for the participants with dementia.Therefore, blinding was not possible.Physicians checked patients' eligibility (age Ն70 years, community dwelling, and screened positive for dementia 33 ), informed them about the study, and asked for written informed consent.

CDCM Intervention
The CDCM intervention was developed according to dementia-specific guidelines, [34][35][36][37] targeting the individual participant level, and was delivered in participants' homes by specifically qualified nurses for 6 months, aiming to support participants living with dementia and their caregivers through coordination and management of individualized optimal treatment and care within the health and social care system. 26,27The main intervention pillars were (1) management of individualized treatment and care, (2) medication management, and (3) caregiver support.After a standardized, comprehensive assessment of patients' and caregivers' unmet needs, the nurses generated an individualized intervention task list, discussed these tasks in an interdisciplinary case conference (nursing scientist, neurologist or psychiatrist, psychologist, and pharmacist) and with the treating GP, and carried out tasks in cooperation with the GP and various health and social care practitioners over 6 months.The medication management system 38 generated recommendations for GPs concerning antidementia drugs, drug-related problems, interactions, and adverse events.The nurses monitored the task completion in 6 home visits with an average duration of 1 hour.Intervention feedback from GPs was documented, indicating high agreement. 39e intervention was supported by an information technology-and algorithm-based intervention management system, enabling swift systematic identification of needs and implementation and monitoring of intervention tasks.38,40

Outcomes
Nurses conducted assessments at baseline and at 12, 24, and 36 months.Assessments consisted of standardized, computer-assisted, face-to-face interviews at the participant's or caregiver's home.

Clinical Outcomes
Primary study outcomes included the following assessments.Behavioral and psychological symptoms were measured by the Neuropsychiatric Inventory (NPI; score range 1-144, with higher scores indicating greater severity and frequency of neuropsychiatric symptoms, a proxy rating given by caregivers on 12 dimensions of neuropsychiatric behaviors among people living with dementia). 41regiver burden was measured by the Berlin Inventory of Caregivers' Burden in Dementia (BIZA-D; score range 0-4, with higher scores indicating greater caregiver burden), with the subdomain "individual limitation and health" summarizing lack of energy, perceived physical and mental burden of informal care, and limitations in the realization of one's own needs.42 Health-related QOL was measured by the Quality of Life in Alzheimer Disease scale (QOL-AD; score range 1-4, with higher scores indicating better QOL), a disease-specific measure of HRQOL with 13 dimensions, 43 and by the 12-Item Short-Form Health Survey (SF-12; score range 0-100, with higher scores indicating better health), 44 a generic, multidimensional instrument assessing physical (Physical Component Summary [PCS]) and mental (Mental Component Summary [MCS]) health.Contrary to the trial protocol, the SF-12 was used to assess the association with mental and physical health separately.Prescription of antidementia drugs (donepezil, galantamine, rivastigmine, and memantine) and potentially inappropriate medications according to the PRISCUS criteria 45 was also assessed.

Secondary outcomes were cognitive impairment according to the Mini-Mental State
Examination (score range 0-30, with higher scores indicating better cognition), 46 depression according to the 15-item Geriatric Depression Scale (score range 0-15, with higher scores indicating worse depression), 47 and functional impairment according to the Bayer Activities of Daily Living Scale (B-ADL; score range, 0-10, with higher scores indicating worse functional status). 48

Cost-Effectiveness Outcomes
The cost-effectiveness analysis was based on a preference-based scoring algorithm converting SF-12 responses to health utilities (Short Form 6-Dimension algorithm [SF-6D]) anchored at 0 (death) and 1 (full health) to calculate quality-adjusted life-years (QALYs).The analysis also considered health care utilization using the Resource Utilization in Dementia questionnaire, 49 completed by caregivers and health services practitioners, and medical records (eTable 4 in Supplement 2).

Statistical Analysis
This secondary analysis deviated from the trial protocol by extending the time horizon to 36 months. 25Data were analyzed from March 2011 to March 2018 using Stata, version 16 (StataCorp LLC).Two-sided P < .05 was considered significant.
In addition to clinical variables, demographics (age, sex, and living situation), comorbidities (number of diagnoses listed in GP files, Charlson Comorbidity Index), and the number of drugs regularly taken were used for sample description and model adjustments.Study group differences at baseline were assessed using generalized linear and logistic models with random effects for clusters (GP practices).Missing data were handled using multiple imputations by chained equations (eAppendix 1 in Supplement 2). 50,51

Clinical Outcome Analyses
Descriptive statistics and t tests were used to describe and compare outcomes between groups.
Calculated effect sizes (Cohen d, Cramér V) between groups were classified as small (Cohen d = 0.2; Cramér V = 0.1), medium (Cohen d = 0.5; Cramér V = 0.3), or large (Cohen d = 0.8; Cramér V = 0.5). 52We performed multivariable linear regression models for 12-, 24-, and 36-month associations with the outcome variable (nonstandardized and z-standardized) as a dependent variable and the study group as the variable of interest.The outcome baseline value was included as a covariate to account for interindividual variance and to reduce residual variance.Age, sex, and living situation (alone vs not alone) were included as covariates.Due to a declining number of patients per cluster with increasing study duration, random effects were only considered when the intraclass correlation for the respective outcome was higher than 0.3 (eAppendixes 2 and 3 in Supplement 2). 53

Cost-Effectiveness Analysis
Costs were calculated from a public payer perspective in 2023 values in euros ($1.08 = €1) based on health care utilization and unit costs 54,55 (eTable 3 in Supplement 2).The health utilities and day of death were used for QALY calculation (eAppendix 4 in Supplement 2).In cases of death, from the day of death, health utilities and costs were set to 0. Quality-adjusted life-years and costs were discounted at 3.5% per annum.
The incremental cost-effectiveness ratio (ICER) was calculated using the incremental cost per QALY gained by the CDCM compared with usual care. 56Due to baseline differences in functional impairment, which is associated with costs, 57 incremental costs and QALYs were estimated using linear regression models adjusted for age, sex, living situation, and functional impairment. 58,59To handle sampling uncertainty in the ICER, nonparametric bootstrapping with 1000 resamples stratified for group distribution was used. 60

Sensitivity Analyses
Sensitivity analyses were used to test the robustness of results.These included complete case analysis, truncating cost outliers (99th percentile) to minimize the impact of patients with high costs, and subgroup analysis for people living with dementia who were living alone at home vs not living alone for exploratory purposes, since caregiver availability could affect the CDCM cost-effectiveness.

Patient Characteristics
A total of 6838 people were screened at 128 GP practices; 1166 fulfilled the eligibility criteria, 634 agreed to participate, and 516 started the baseline assessment.A total of 174 participants withdrew their informed consent, 139 died, and 10 suspended the assessments until the 3-year follow-up.
A  e BADL score range, 0 to 10, with higher scores indicating more functional deficits.

Cost-Effectiveness
f Based on the number of ICD-10 diagnoses recorded in the medical record of the treating general practitioner.
g Low was indicated by 0 to 2 points; high, 3 to 4 points; and very high, more than 4 points.
h Drugs needing to be taken regularly, based on cabinet review at patients' homes.

Discussion
This study adds evidence for the effectiveness and cost-effectiveness of a 6-month collaborative care intervention for people living with dementia, demonstrating that CDCM was positively associated with behavioral and psychological symptoms, mental health, and caregiver burden over 36 months.
Also, CDCM was likely to have been cost-effective, especially for people with dementia living alone.
Addressing behavioral and psychological symptoms in dementia is a clinical priority, but symptom management and alleviation are challenging.A meta-analysis by Reilly et al 17 demonstrated that CDCM was associated with significantly reduced symptoms at 18 months (standardized mean difference, −0.35 [95% CI, −0.63 to −0.07]).We found that CDCM was consistently and clinically meaningfully 41 positively associated with behavioral and psychological symptoms at 12, 24, and 36 months with moderate effect sizes, extending the current evidence.While symptoms steadily deteriorated in control individuals, the CDCM intervention of tailoring nonpharmacologic and pharmacologic approaches to the individual's specific needs stabilized behavioral and psychological symptoms beyond the intervention period. 61,62other goal of CDCM is to stabilize caregiver burden.Evidence from 2 studies suggests that CDCM can minimize caregiver burden with small effect sizes at 6 and 12 months. 20,63In another study, effects at 18 months or after were uncertain. 17We found a significantly lower caregiver burden after 12 and 36 months with moderate effect sizes.The absence of midterm differences at 24 months in previous studies 17,20,63 and the minor differences in our study could be attributed to the intervention duration, usually 6 months or less.Addressing existing unmet needs during the intervention and carrying out interventions that better prepare people living with dementia and their caregivers in advance could have an immediate and lasting impact when the disease progresses.
There was a trend for delayed institutionalization in the first and second year, followed by more frequent institutionalization in the third year in the intervention group, predominately for those living alone, which aligns with previous studies. 17Studies have revealed a decrease in caregiver burden immediately after institutionalization of people living with dementia, 64,65 potentially explaining the large effect sizes in the current study at 36 months in the caregiver burden scale and behavioral and psychological symptoms.Both are caregiver ratings incorporating the caregiver burden.Our results align with these findings.However, other studies did not find effects on HRQOL. 19,68In this study, CDCM was associated with stabilized mental health over 36 months, whereas mental health continuously deteriorated in control individuals.Previous studies 19,68 used HRQOL measures that summarized different domains into one without finding any effect.Assessing physical and mental health separately enables a differentiated view of the CDCM's efficacy for HRQOL.
Concerning the economic outcomes, pooled data from 2 studies 69,70 demonstrated that CDCM significantly reduced costs at 12 months.Preliminary data from the D-CARE study demonstrated that CDCM reduced hospitalization, delayed institutionalization, and lowered costs over 18 months. 21,71r results align with these studies, indicating cost savings after 1 and 2 years attributable to lower Study enrollment started on January 1, 2012, and ended on December 31, 2014.The 36-month follow-up was completed on March 31, 2018.Participants were included if they completed at least 2 of 3 annual assessments.Patients who died were included in the cost-effectiveness analyses.The trial flowchart and the results of dropout analyses are given in eFigure 1 and eTables 1 and 2 in Supplement 2.

Figure 2 .0
Figure 2. Cost-Effectiveness Plane and Acceptability Curves for Collaborative Dementia Care Management (CDCM) vs Usual Care

Table 1 .
Baseline Participant Characteristics of the Sample for the Clinical Outcome Analysis Available After 3 Years Total costs after 36 months were 31 396€ (95% CI, 28 234€-34 558€) (US $34 222 [95% CI, $30 775-$37 668]) for the CDCM group and 30 959€ (95% CI, 26 024€-35 894€) (US $33 745 [95% CI, a Data are presented as number (percentage) of participants unless otherwise indicated.b Clinical Outcomes and Cost-Effectiveness of Collaborative Dementia Care $28 366-$39 124]) for the usual care group.The CDCM intervention was associated with significantly increased medication and medical aid costs but with lower costs in all other cost categories, especially for hospitalizations.There was no association with institutionalization after 36 months.

Table 3 .
Unadjusted and Adjusted Mean Cost and Differences and Incremental Cost-Effectiveness RatioPertaining to patients' HRQOL, studies of CDCM outcomes have reported better HRQOL over 12 and 18 months.
a For statistical comparison between groups, t tests (unadjusted means) and multivariate regression models adjusted for age, sex, and functional impairment at baseline (adjusted means) were calculated.bP< .10. c P < .05. d To convert to US dollars, multiply by 1.09.JAMA Network Open | GeriatricsClinical Outcomes and Cost-Effectiveness of Collaborative Dementia Care JAMA Network Open.2024;7(7):e2419282.doi:10.1001/jamanetworkopen.2024.19282(Reprinted) July 5, 2024 10/17 Downloaded from jamanetwork.comby guest on 07/07/2024 ). B, Curves indicate the likelihood that the intervention is cost-effective at the given threshold if society has a willingness to pay (WTP) a certain amount per QALY.Vertical dashed lines (WTP [λ] values) indicate WTP thresholds of 40 000€, 80 000€, and 160 000€ per QALY.To convert euros to US dollars, multiply by 1.09.Drop-Out Analysis for Patients Excluded From Outcome and Cost-Effectiveness Analysis eTable 2. Drop-Out Analysis for Patients Who Dropped Out After Completing the Baseline Assessment Before Follow-Up at Years 1, 2, and 3 eTable 3. Cost Calculation for the Implementation of 1 Nurse Carrying Out the Collaborative Dementia Care Management for 90 Patients per Year eTable 4. Cost Categories and Unit Costs for Monetary Valuation of Medical and Formal Health Care Resources and Services eTable 5. Regression Analyses for the Treatment Effect of CDCM vs Usual Care eTable 6. Regression Analyses for the Treatment Effect of CDCM vs Usual Care Separately Over Years for Complete Cases eTable 7. Regression Analyses for the Treatment Effect of CDCM vs Usual Care Separately Over 1, 2, and 3 Years eTable 8. Adjusted Incremental Cost and Effects of CDCM vs Usual Care for Year 1, 2, 3, and Cumulative eTable 9. Unadjusted Health Care Resource Utilization, Cost, and Quality-Adjusted Life of CDCM vs Usual Care for Year 1, 2, 3, and Cumulative eTable 10.Adjusted Incremental Cost and Effects on QALYs of the Collaborative Model of Dementia Care vs Usual Care for Year 1, 2, 3, and Cumulative, Separately for Those Living Alone and Not Living Alone eTable 11.Comparison of the Participant Characteristics at Baseline and 3 Years After Baseline eFigure 1. Flow Chart of the DelpHi-MV Trial eFigure 2. Cost-Effectiveness Acceptability Curves of the Scenario Analyses eFigure 3. Cost-Effectiveness Plane and Cost-Effectiveness Acceptability Curves of the CDCM vs Usual Care After 3 Years, Shown Separately for Patients Living Alone and Not Living Alone eAppendix 1. Methods Used to Handle Missing Data and That Used Stata Code eAppendix 2. Intraclass Correlation and Design Effects for Each Outcome and Time Point eAppendix 3. Standardized Measure of Effect Size for Each Outcome and Time Point eAppendix 4. Calculation of Utility Values and Quality-Adjusted Life-Years